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Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
Novel agents for the treatment of resistant Gram-positive infections
1Antibiotic Resistance Monitoring and Reference Laboratory, 61 Colindale Avenue, London NW9 5HT, UK. nwoodford@phls.org.uk
Abstract:
Bacteria have proved themselves able to develop resistance to every antibiotic used clinically. Traditional agents used for treatment of serious infections caused by Gram-positive species have recently been supplemented with the introduction of linezolid, quinupristin-dalfopristin, several new quinolones and telithromycin. However, resistance to many of these agents has already been reported and, although each currently retains activity against the vast majority of clinical isolates of its target species, their long-term efficacy is uncertain. We must look to develop other compounds to replace and hopefully improve upon existing anti-Gram-positive agents. Daptomycin (a lipopeptide), oritavancin and dalbavancin (both second-generation glycopeptides) and ramoplanin (a glycolipodepsipeptide) are among the agents in advanced stages of development and, at present, many seem likely to proceed to licensing. In addition, it is encouraging that many agents active against novel bacterial targets have been discovered and are in earlier stages of development. In the next two decades, we should be optimistic that a regular flow of new anti-Gram-positive agents will enable us to offset the constant spectre of bacterial resistance.
Insights
Bacterial resistance to antibiotics is a growing concern. New anti-Gram-positive agents are in development to combat this threat and ensure future treatment efficacy.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Bacterial resistance to antibiotics is a significant clinical challenge, necessitating the development of novel therapeutic agents.
- Existing antibiotics, including linezolid and new quinolones, face emerging resistance, threatening their long-term effectiveness against Gram-positive infections.
Purpose of the Study:
- To review the current landscape of anti-Gram-positive agents and highlight emerging therapies.
- To discuss the development of new compounds to overcome antibiotic resistance in Gram-positive bacteria.
Main Methods:
- Literature review of existing and novel anti-Gram-positive antibiotics.
- Analysis of agents in advanced stages of development and those in earlier research phases.
Main Results:
- Several new agents, including daptomycin, oritavancin, dalbavancin, and ramoplanin, are in late-stage development and nearing licensing.
- Discovery of agents targeting novel bacterial pathways offers promise for future antibiotic pipelines.
Conclusions:
- A continuous pipeline of new anti-Gram-positive agents is crucial to combat the evolving threat of bacterial resistance.
- Optimism exists for sustained therapeutic options against Gram-positive infections over the next two decades due to ongoing research and development.
